Controlling Blood Pressure in Treatment Resistant Hypertension: A Pilot Study. Background: Treatment resistant hypertension (TRH), i.e., blood pressure (BP) above goal on >3 BP medications affects millions of people and contributes to health disparities. In clinical trials, where patient compliance is confirmed and BP meds are systematically titrated to attain control, ~20% of patients have TRH, which suggests limited effectiveness of current treatment strategies contributes to TRH. This pilot study examines the feasibility, safety, and preliminary effectiveness of four evidence-based approaches to improving BP control in TRH. The four strategies include adding an aldosterone antagonist in eligible patients (AAEP), renin treatment-guided therapeutics (RTGT), clinical hypertension specialist care (CHSC), and RTGT+CHSC. Hypothesis: Defining pathophysiological mechanisms (RTGT) and/or expert consultation (CHSC) will improve BP control more than 'blindly'adding an aldosterone antagonist in eligible patients (AAEP). Specific aim: Assess the feasibility, safety, and preliminary comparative effectiveness in a diverse group of patients and clinical settings of four evidence-based treatment strategies for treatment resistant hypertension (TRH) to test the hypothesis that RTGT and/or CHSC are more effective than AAEP for controlling BP in TRH. Hypothesis: Eliciting patient, provider and staff experiences and insights post intervention will identify barriers and facilitators to implementing AAEP, RTGY, and CHSC that will inform design of the demonstration study. Specific Aim. Conduct post-intervention patient questionnaires and interviews and staff and provider focus groups and an online SWOT to identify barriers and facilitators to AAEP, RTGY and CHSC that will inform the demonstration study in real world practice settings. Methods: 8 diverse clinics (>1 community health centers, single &multi-site primary care clinics, community residency training programs) that provide care for a diverse patient population will be randomized to 1 of 4 study arms. Each cilnic will enroll 18 TRH patients (36/arm). All clinics receive BpTRU monitors and training to standardize BP measurements and 'eliminate'white coat hypertension. Key study data include patient demographics, visits, BP values, meds, and lab data. Post study focus groups and strengths, weaknesses, opportunities, threats (SWOT) analysis with providers and staff and patient questionnaire and interviews will be used to evaluate several dimensions of the study and guide the demonstration study design. Significance: TRH is common medical condition, and relatively ineffective treatment regimens are a significant contributing factor. The long-term goal is to establish practical, effective, and widely replicable approaches for controlling BP in TRH and reducing clinical complications and related health disparities. (End of Abstract) PUBLIC HEALTH RELEVANCE: Treatment resistant hypertension (TRH) is common medical condition, and relatively ineffective treatment regimens are a significant contributing factor. The long-term goal of the proposed research is to establish practical, effective, and widely replicable approaches for controlling blood pressure in TRH and reducing the associated clinical complications and health disparities.